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Chemoprevention of colorectal cancer targeting mutated K-ras in ACF

Research Project

Project/Area Number 14370187
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Gastroenterology
Research InstitutionSapporo Medical University

Principal Investigator

NIITSU Yoshiro  Sapporo Medical University, Professor, 医学部, 教授 (10045502)

Co-Investigator(Kenkyū-buntansha) KATO Junnji  Sapporo Medical University, Associate Professor, 医学部, 助教授 (20244345)
TAKAYAMA Tetsuji  Sapporo Medical University, Assistant Professor, 医学部, 講師 (10284994)
Project Period (FY) 2002 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥13,600,000 (Direct Cost: ¥13,600,000)
Fiscal Year 2003: ¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 2002: ¥9,800,000 (Direct Cost: ¥9,800,000)
Keywordscolorectal cancer / Chemoprevention / K-ras
Research Abstract

Aim : We previously demonstrated that aberrant crypt foci(ACF) are precursors of adenoma-carcinoma sequence in colorectal carcinogenesis, and ACF are frequently positive for K-ras mutation. In this study, we examined the inhibitory effect of FTI and GGTI targeting mutated K-ras in ACF. Methods : P344 rats were administered with colorectal carcinogen(dimethylhydralazine ; DMH). FTI-287 or GGTI-297 were intraperioneously injected to the rats, and they were sacrificed at 8 weeks for examination of ACF and 24 weeks for polyps. ACF identification was performed by methyleneblue staining under stereoscopic microscope. Results : The rats treated with FT1276 showed reduced number of ACF in a dose dependent manner. Treatment with 70mg/kg significantly reduced the number of ACF. Treatment with GGT1297 showed similar tendency. There was a synergistic inhibitory effect in FTI-276 and GGTI-297 treatment in the rats model of colon carcinogenesis. The adverse effects of FTI-276 and GGTI-297 were negligible. Conclusion : It was suggested that FTI and GGTI are useful chemopreventive agents targeting mutated K-ras in ACF of colorectal carcinogenesis.

Report

(3 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • Research Products

    (19 results)

All Other

All Publications (19 results)

  • [Publications] Sagawa T, Takayama T, Niitsu Y, et al.: "Argon plasma coagulation for successful treatment of early gastric cancer with intramucosal invation"GUT. 52. 334-339 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Nakajima T, Takayama T, Niitsu Y, et al.: "Reversal of Multiple Drug Resistance in Cholangiocarcinoma by the GST-π Specific Inhibitor : O^1-Hexadecyl γ-glutamyl-S-benzylcysteinyl-D-phenylglycine ethyl ester"Journal of Pharmacology Experimental Therapeutics. 306. 863-869 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Terui T, Takayama T, Niitsu Y, et al.: "Induction of PIG3 and NOXA through acetylation of p53 at 320 and 373 lysine residues as a mechanism for apoptotic cell death by histone deacetylase inhibitors"Cancer Research. 63. 8948-8954 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Matsunaga T, Kato J, Niitsu Y, et al.: "Interaction between leukemic-cell VLA-4 and stromal fibronectin is a decisive factor for minimal residual disease of acute myelogenous leukemia"Nature Medicine. 52. 334-339 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yamauchi A, Ito Y, Niitsu Y, et al.: "Pre-administration of angiopoietin-1 followed by VEGF induces functional and mature vascular formation in a rabbit ischemic model"Journal Gene Medicine. 5. 994-1004 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Sagawa T, Takayama T, Oku T, Hayashi T, Ohta H, Okamoto T, Muramatsu H, Katsuki 5, Sato Y, Kato J, Niitsu Y.: "Argon plasma coagulation for successful treatment of early gastric cancer with intramucosal invation."Gut.. 52. 334-339 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Nakajima T, Takayama T, Miyanishi K, Nobuoka A, Thayashi T. Abe T, Kato J, Sakon K, Naniwa Y, Tanabe H, Niitsu Y.: "Reversal of Multiple Drug Resistance in Cholangiocarcinoma by the GST-π Specific Inhibitor : O^1-Hexadecyl γ-glutamyl-S-benzylcysteinyl-D-phenylglycine ethyl ester."J Pharmacology Exp Ther. 306. 861-869 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Terui T, Murakarni K, Takimoto R, Takahashi M, Takada K, Murakami T, Minami S, Matsunaga T, Takayama T, Kato I, Niitsu Y.: "Induction of PIG3 and NOXA through acetylation of p53 at 320 and 373 lysine residues as a mechanism for apoptotic cell death by histone deacetylase inhibitors."Cancer Res.. 63. 8948-8954 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Matsunaga T, Takemoto N, Sato T, Takimoto R, Tanaka I, Fujimi A, Akiyama T, Kuroda H, Kawano Y, Kobune M, Kato J, Hirayama Y, Sakamaki S, Kohda K, Miyake K, Niitsu Y.: "Interaction between leukemic-cell VLA-4 and stromal fibronectin is a decisive factor for minimal residual disease of acute myelogenous leukemia."Nat Med.. 9. 1158-1165 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yamauchi A, Ito Y, Morikawa M, Kobune M, Huang I, Sasaki K, Takahashi K, Nakamura K, Dehari H, Niitsu Y, Abe T, Hamada H.: "Pre-administration of angiopoietin-1 followed by VEGF induces functional and mature vascular formation in a rabbit ischemic model."J Gene Med.. 5. 994-1004 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Sagawa T, Takayama T, Niitsu Y, et al.: "Argon plasma coagulation for successful treatment of early gastric cancer with intramucosal invation"GUT. 52. 334-339 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Nakajima T, Takayama T, Niitsu Y, et al.: "Reversal of Multiple Drug Resistance in Cholangiocarcinoma by the GST-π Specific Inhibitor : O^1-Hexadecyl γ-glutamyl-S-benzylcysteinyl-D-phenylglycine ethyl ester"Journal of Pharmacology Experimental Therapeutics. 306. 863-869 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Terui T, Takayama T, Niitsu Y, et al.: "Induction of PIG3 and NOXA through acetylation of p53 at 320 and 373 lysine residues as a mechanism for apoptotic cell death by histone deacetylase inhibitors"Cancer Research. 63. 8948-8954 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Matsunaga T, Kato J, Niitsu Y, et al.: "Interaction between leukemic-cell VLA-4 and stromal fibronectin is a decisive factor for minimal residual disease of acute myclogenous leukemia"Nature Medicine. 52. 334-339 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Yamauchi A, Ito Y, Niitsu Y, et al.: "Pre-administration of angiopoietin-1 followed by VEGF induces functional and mature vascular formation in a rabbit ischemic model"Journal Gene Medicine. 5. 994-1004 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Takayama T, Niitsu Y, et al.: "Ananlysis of K-ras, APC and β-catenin in aberrnt crypt foci in patients with adenorma and cancer, and familial adenomatous polyposis"Gastroenterology. 121. 599-611 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] Miyanishi K, Takayama T, Niitsu Y, et al.: "Glutathione transferase-π overexpression is closely associated with K-ras mutation during human colon carcinogenesis"Gastroenterology. 121. 865-874 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kato J, Takayama T, Niitsu Y et al.: "Normalization of elevated hepatic 8-hydroxy-2' Deoxyguanosine levels in chronic hepatitis C patients by phrebotomy and low iron diet"Cancer Reserch. 61. 8697-8702 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kato J, Niitsu Y, et al.: "Ratio of transferrin (Tf) to Tf-receptor complex in circulation differs depending on Tf iron saturation"Clin Chem.. 48. 181-183 (2002)

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2021-08-24  

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